Myocardial infarction (MI) is a significant cause of morbidity and mortality in the U.S. H2 Relaxin (H2R) is a Phase III clinical trial-stage peptide that exhibits both anti-inflammatory and cytoprotective activities which can potentially be harnessed for the treatment of MI via use as adjuvant to recanalization therapy. However, clinical administration of rhH2R is not only prohibitively expensive but also plagued by numerous logistical issues. To fully capitalize on the therapeutic potential of the H2R pathway while overcoming the afore-mentioned shortcomings, Angion Biomedica Corp. has developed a library of chemically synthesizable H2R-like peptides. In preliminary studies, ANG-4011, our lead H2R-like peptide demonstrated significant tissue protective effects. The present Phase 1 SBIR proposal is designed to fully optimize the therapeutic effects of ANG-4011 in experimental myocardial ischemia-reperfusion injury. Data from this program will form the basis for a comprehensive SBIR Phase II program goals for which include optimization of ANG-4011 delivery in sustained-release, clinically compatible, biodegradable microspheres, evaluation of ANG-4011 therapy in myocardial-reperfusion models accompanied by co-morbidities (e.g. age and diabetes) and ANG-4011 safety/toxicology evaluation. The overall objective of this program is to bring potentially promising therapeutic to clinical trials for patients presenting with MI. PUBLIC HEALTH RELEVANCE: Myocardial infarction remains a significant cause of morbidity and mortality. A cardioprotective agent that reduces infarct size and salvages myocardium can avert the transition to pump failure.